The Impact of Age and Sex on Mouse Models of Melioidosis

Abstract

Mouse models have been used to generate critical data for many infectious diseases. In the case of Burkholderia pseudomallei, mouse models have been invaluable for bacterial pathogenesis studies as well as for testing novel medical countermeasures including both vaccines and therapeutics. Mouse models of melioidosis have also provided a possible way forward to better understand the chronicity associated with this infection, as it appears that BALB/c mice develop an acute infection with B. pseudomallei, whereas the C57BL/6 model is potentially more suggestive of a chronic infection. Several unanswered questions, however, persist around this model. In particular, little attention has been paid to the effect of age or sex on the disease outcome in these animal models. In this report, we determined the LD 50 of the B. pseudomallei K96243 strain in both female and male BALB/c and C57BL/6 mice in three distinct age groups. Our data demonstrated a modest increase in susceptibility associated with sex in this model, and we documented important histopathological differences associated with the reproductive systems of each sex. There was a statistically significant inverse correlation between age and susceptibility. The older mice, in most cases, were more susceptible to the infection. Additionally, our retrospective analyses suggested that the impact of animal supplier on disease outcome in mice may be minimal. These observations were consistent regardless of whether the mice were injected with bacteria intraperitoneally or if they were exposed to aerosolized bacteria. All of these factors should be considered when designing experiments using mouse models of melioidosis.Pathogens 2020, 9, 113 2 of 18 has clearly demonstrated that it is quickly becoming a global concern [1-4]. B. pseudomallei can infect humans and animals via several routes of infection (i.e., inhalation of aerosolized bacteria, ingestion of contaminated drinking water, or through inoculation of a subcutaneous lesion) [5][6][7][8][9]. Inhalational melioidosis has been associated with monsoonal rains in endemic areas and is also a primary concern in the biodefense research community [10,11]. Pneumonia is a common presentation, which can be caused by a primary introduction of aerosolized bacteria into the lungs or a secondary pneumonia resulting from hematogenous spread to the lungs after a primary infection elsewhere [12,13]. There are currently no approved vaccines for B. pseudomallei and antibiotic treatment can be hampered by non-specific symptomology, the protracted two-phase course of treatment required, and the high rate of naturally occurring antibiotic-resistant strains [14,15]. Because of the public health and biodefense concerns associated with this bacterium, efforts are underway to develop effective medical countermeasures [15,16]. Accordingly, appropriate and well-characterized animal models are required for the development and testing of such efforts.The mouse model has afforded many research groups the opportunity to characterize the pathogen...

Osteomyelitis and Septic Arthritis Due to Burkholderia pseudomallei: A 10-Year Retrospective Melioidosis Study From South China

“…A marked male predominance is observed in melioidosis studies (Gassiep et al, 2020;Klimko et al, 2020;Wu et al, 2020). It was infrequently documented that female was overrepresented in the bone and joint cohort (Weerachai Kosuwon, 2003).…”

Layered and integrated medical countermeasures against Burkholderia pseudomallei infections in C57BL/6 mice

“…In this study we used only female mice. We have previously shown that female and male mice are similar regarding disease course but females are preferred for long course studies due to aggression patterns and self-injury in male mice that often require early euthanasia intervention ( Klimko et al, 2020 ). For challenge studies mice were exposed to aerosolized B. pseudomallei K96243 on day 32 (±3) post-last vaccination, as described previously ( Bearss et al, 2017 ; Trevino et al, 2018 ).…”

Efficacy of Treatment with the Antibiotic Novobiocin against Infection with Bacillus anthracis or Burkholderia pseudomallei

“…BALB/c mice are a highly susceptible model for acute melioidosis [ 24 , 25 , 26 , 28 ]. Female mice which were 7 to 9 weeks of age at time of exposure were used in both models, in part due to the aggressive and injury-inducing behavior of males, which can confound results in long-duration studies such as those with B. pseudomallei [ 57 ]. Doses given by IP routes were administered in a total volume of 200 µL.…”